Cartilage is a very specialized tissue containing only one cell type, the chondrocyte. Chondrocyte metabolism and function are influenced by the composition of the extracellular environment (Oxygen tension, pH, ionic concentration), the extracellular matrix composition, the matrix-cell interactions and the physical signals (stress and stain) transmitted across the articular surfaces of the joint. The failure of cartilage to regenerate itself is felt to be one of the fundamental pathways in the pathophysiology of degenerative osteoarthritis. The goal of this study is to examine the reparative potential of chondrocytes taken from aging non-human primates at various stages of joint degeneration. The atomic force microscope (AFM) will be used to map the surface topography, collagen structural lattice and the mechanical properties of intact articular cartilage. Similarly, the matrix-forming potential of chondrocytes isolated from the knees and hands of these animals will be investigated. Progress during the past year: Initial work on this project started in April 2004. To date, approximately twenty pairs of non-human primate knees and hands have been collected from the NIH tissue bank. Several of the specimens have been imaged by micro-CT and micro-MRI. In recent months, our quantitative and qualitative assessment of articular cartilage using the AFM, have confirmed the feasibility of the proposed studies. Previous reports have confirmed the successful use of AFM to visualize the collagen fibril network of bovine cartilage. Given this unique opportunity for the nondestructive manipulation of the cartilage surface, the chondrocyte cytoskeleton, and the subchondral bone. We propose to study the following; during the next year: To use AFM images and force data to demonstrate the alterations or deformations of the cartilage ECM, and of the chondrocyte morphology. To assess the functional properties of both intact cartilage tissues, and the isolated chondrocytes. To use AFM to examine the physical properties (lubrication, sheer stress, surface charge, elasticity, collagen fiber size and orientation) of aging articular cartilage. To assess and/or quantitate these characteristics as a function of tissue and cellular aging as it relates to OA.